scholarly journals The Dichotomous Role of Bone Marrow Derived Cells in the Chemotherapy-Treated Tumor Microenvironment

2020 ◽  
Vol 9 (12) ◽  
pp. 3912
Author(s):  
Avital Vorontsova ◽  
Tal Kan ◽  
Ziv Raviv ◽  
Yuval Shaked
Keyword(s):  
Bone Marrow ◽  
Tumor Microenvironment ◽  
Immune Modulation ◽  
Therapy Resistance ◽  
Therapy Outcomes ◽  
Primary Tumors ◽  
Combination Treatments ◽  
Response To Chemotherapy ◽  
Metastatic Process ◽  
Bone Marrow Derived Cells

Bone marrow derived cells (BMDCs) play a wide variety of pro- and anti-tumorigenic roles in the tumor microenvironment (TME) and in the metastatic process. In response to chemotherapy, the anti-tumorigenic function of BMDCs can be enhanced due to chemotherapy-induced immunogenic cell death. However, in recent years, a growing body of evidence suggests that chemotherapy or other anti-cancer drugs can also facilitate a pro-tumorigenic function in BMDCs. This includes elevated angiogenesis, tumor cell proliferation and pro-tumorigenic immune modulation, ultimately contributing to therapy resistance. Such effects do not only contribute to the re-growth of primary tumors but can also support metastasis. Thus, the delicate balance of BMDC activities in the TME is violated following tumor perturbation, further requiring a better understanding of the complex crosstalk between tumor cells and BMDCs. In this review, we discuss the different types of BMDCs that reside in the TME and their activities in tumors following chemotherapy, with a major focus on their pro-tumorigenic role. We also cover aspects of rationally designed combination treatments that target or manipulate specific BMDC types to improve therapy outcomes.

scholarly journals Targeting E-selectin to Tackle Cancer Using Uproleselan

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 335
Author(s):  
Barbara Muz ◽  
Anas Abdelghafer ◽  
Matea Markovic ◽  
Jessica Yavner ◽  
Anupama Melam ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Metastatic Tumor ◽  
Therapy Resistance ◽  
Surface Proteins ◽  
Cell Trafficking ◽  
Primary Role ◽  
Novel Therapy ◽  
Tumor Dissemination

E-selectin is a vascular adhesion molecule expressed mainly on endothelium, and its primary role is to facilitate leukocyte cell trafficking by recognizing ligand surface proteins. E-selectin gained a new role since it was demonstrated to be involved in cancer cell trafficking, stem-like properties and therapy resistance. Therefore, being expressed in the tumor microenvironment, E-selectin can potentially be used to eradicate cancer. Uproleselan (also known as GMI-1271), a specific E-selectin antagonist, has been tested on leukemia, myeloma, pancreatic, colon and breast cancer cells, most of which involve the bone marrow as a primary or as a metastatic tumor site. This novel therapy disrupts the tumor microenvironment by affecting the two main steps of metastasis—extravasation and adhesion—thus blocking E-selectin reduces tumor dissemination. Additionally, uproleselan mobilized cancer cells from the protective vascular niche into the circulation, making them more susceptible to chemotherapy. Several preclinical and clinical studies summarized herein demonstrate that uproleselan has favorable safety and pharmacokinetics and is a tumor microenvironment-disrupting agent that improves the efficacy of chemotherapy, reduces side effects such as neutropenia, intestinal mucositis and infections, and extends overall survival. This review highlights the critical contribution of E-selectin and its specific antagonist, uproleselan, in the regulation of cancer growth, dissemination, and drug resistance in the context of the bone marrow microenvironment.

57 Bone Marrow Derived Cells Contribute to the Tumor Microenvironment and Increase the Aggressiveness of Colon Cancer Cells

2009 ◽  
Vol 136 (5) ◽  
pp. A-9-A-10
Author(s):  
Jan Cerny ◽  
Hanchen Li ◽  
Calin Stoicov ◽  
Xueli Fan ◽  
Jian Hua Liu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Colon Cancer ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Colon Cancer Cells ◽  
Bone Marrow Derived Cells

scholarly journals Pre-metastatic Niche Formation in Different Organs Induced by Tumor Extracellular Vesicles

2021 ◽  
Vol 9 ◽  
Author(s):  
Qi Dong ◽  
Xue Liu ◽  
Ke Cheng ◽  
Jiahao Sheng ◽  
Jing Kong ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Extracellular Vesicles ◽  
Critical Role ◽  
Matrix Remodeling ◽  
Metastatic Niche ◽  
Primary Tumors ◽  
Target Organs ◽  
Bone Marrow Derived Cells ◽  
Metastatic Microenvironment ◽  
Underlying Mechanisms

Primary tumors selectively modify the microenvironment of distant organs such as the lung, liver, brain, bone marrow, and lymph nodes to facilitate metastasis. This supportive metastatic microenvironment in distant organs was termed the pre-metastatic niche (PMN) that is characterized by increased vascular permeability, extracellular matrix remodeling, bone marrow-derived cells recruitment, angiogenesis, and immunosuppression. Extracellular vesicles (EVs) are a group of cell-derived membranous structures that carry various functional molecules. EVs play a critical role in PMN formation by delivering their cargos to recipient cells in target organs. We provide an overview of the characteristics of the PMN in different organs promoted by cancer EVs and the underlying mechanisms in this review.

scholarly journals Spatiotemporal control of gene expression in bone-marrow derived cells of the tumor microenvironment induced by MRI guided focused ultrasound

Oncotarget ◽  
2015 ◽  
Vol 6 (27) ◽  
pp. 23417-23426 ◽  
Author(s):  
Pierre-Yves Fortin ◽  
Matthieu Lepetit-Coiffé ◽  
Coralie Genevois ◽  
Christelle Debeissat ◽  
Bruno Quesson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Tumor Microenvironment ◽  
Focused Ultrasound ◽  
Control Of Gene Expression ◽  
Bone Marrow Derived Cells ◽  
Mri Guided ◽  
Spatiotemporal Control

scholarly journals Chemotherapy resistance and stromal targets in breast cancer treatment: a review

2020 ◽  
Vol 47 (10) ◽  
pp. 8169-8177
Author(s):  
Y. M. van der Spek ◽  
J. R. Kroep ◽  
R. A. E. M. Tollenaar ◽  
Wilma E. Mesker
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Chemotherapy Resistance ◽  
Tumor Stroma ◽  
Therapy Resistance ◽  
Resistance Mechanisms ◽  
Specific Therapy ◽  
Primary Tumors ◽  
Cytokines And Chemokines

Abstract Therapy resistance is a known problem in breast cancer and is associated with a variety of mechanisms. The role of the tumor microenvironment in cancer development and resistance mechanisms is becoming increasingly understood. Tumor–stroma is the main component of the tumor microenvironment. Stromal cells like cancer-associated fibroblasts (CAFs) are believed to contribute to chemotherapy resistance via the production of several secreted factors like cytokines and chemokines. CAFs are found to influence disease progression; patients with primary tumors with a high amount of tumor–stroma have a significantly worse outcome. Therefore the role of CAFs resistance mechanisms makes them a promising target in anti-cancer therapy. An overview of recent advances in strategies to target breast cancer stroma is given and the current literature regarding these stromal targets is discussed. CAF-specific proteins as well as secreted molecules involved in tumor–stroma interactions provide possibilities for stroma-specific therapy. The development of stroma-specific therapy is still in its infancy and the available literature is limited. Within the scope of personalized treatment, biomarkers based on the tumor–stroma have future potential for the improvement of treatment via image-guided surgery (IGS) and PET scanning.

CARG-2020, an oncolytic artificial virus co-delivering three immunomodulators, to regress and cure established tumors in mice.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14560-e14560
Author(s):  
Bijan Almassian ◽  
Bhaskara R Madina ◽  
Ju Chen ◽  
Marie M Krady ◽  
Xianyong Ma ◽  
...  
Keyword(s):  
Immune Modulation ◽  
Semliki Forest Virus ◽  
Therapeutic Potential ◽  
Complete Response ◽  
Therapy Resistance ◽  
Dominant Negative ◽  
Oncolytic Viruses ◽  
Primary Tumors ◽  
Artificial Virus

e14560 Background: Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in humans. Treatment of late-stage CRC remains ineffective, even with the use of latest immunotherapies. Oncolytic viruses have shown limited use for the treatment of cancers, and further improvement of these agents with immune-modulating activities may prove crucial for patients with CRC and other malignancies. To this end, we developed CARG-2020 as an artificial virus for infectious diseases and immuno-oncology (AVIDIO) that employs virus-like vesicles (VLV). VLVs, which are membrane-encapsulated RNA replicons, are oncolytic and can deliver multiple genes resulting in the modulation of several independent immune pathways. Methods: The AVIDIO platform is comprised of in vitro evolved RNA-dependent RNA polymerase from an alphavirus, Semliki Forest virus, and envelope glycoproteins from vesicular stomatitis virus, which together form VLVs. Unarmed or empty vector (VLV), VLV armed with IL-12 (VLV-IL-12) and a VLV that simultaneously expresses IL-12, a dominant-negative form of IL-17 receptor A (dn-1L17RA) and shRNAs targeting PD-L1 (CARG-2020), were given intratumorally to test their therapeutic potential against established (500-600mm3) MC38 tumors in mice. We used tumor growth measurements and analyses of tumor-infiltrating cells after consecutive treatments with these agents to monitor their antitumor and immunomodulatory activities, respectively. Results: Both VLV-IL-12 and CARG-2020 regressed the tumors to undetectable levels in most mice harboring syngeneic MC38 tumors when given intratumorally. CARG-2020, carrying IL-12, dn-IL17RA and PD-L1 shRNA, exerts broader spectrum of immuno-responses and higher number of complete response rates compared with VLV-IL-12. Treatment of primary tumors with VLV-IL-12 or CARG-2020 also significantly repressed the growth of secondary tumors on the other flank of mouse’s body, suggesting an effective systemic immunity elicited by these two agents against the same type of tumors. In addition to the marked local and systemic activation of Th1 cells and CD8+ T cells by both vectors, CARG-2020 also downregulated PD-L1 expression in tumors, and suppressed expression of IL-17A-activated chemokines CXCL1 and CXCL2 that are known to promote cancer development and therapy resistance. Conclusions: As an oncolytic RNA replicon, AVIDIO platform-derived CARG-2020 encodes IL-12, dn-IL-17RA and PD-L1 shRNAs which are expressed concurrently within the same vector. CARG-2020 modulates IL-12, IL-17RA and PD-L1 signaling, and exerts broad immune modulation in tumor microenvironment. Treatment with CARG-2020 eliminates the majority of grafted large tumors in mice, and is effective against both primary and distal tumors. Based on this impressive efficacy results, further development of CARG-2020 in colorectal patients is warranted.

scholarly journals Changes in the tumor microenvironment and outcome for TME-targeting therapy in glioblastoma: A pilot study

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246646
Author(s):  
Sehar Ali ◽  
Thaiz F. Borin ◽  
Raziye Piranlioglu ◽  
Roxan Ara ◽  
Iryna Lebedyeva ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Macrophage Polarization ◽  
Therapy Resistance ◽  
Therapeutic Agents ◽  
M2 Macrophage ◽  
Targeting Therapy ◽  
Growth And Survival ◽  
Antiangiogenic Therapies ◽  
The Central Nervous System ◽  
Bone Marrow Derived Cells

Glioblastoma (GBM) is a hypervascular and aggressive primary malignant tumor of the central nervous system. Recent investigations showed that traditional therapies along with antiangiogenic therapies failed due to the development of post-therapy resistance and recurrence. Previous investigations showed that there were changes in the cellular and metabolic compositions in the tumor microenvironment (TME). It can be said that tumor cell-directed therapies are ineffective and rethinking is needed how to treat GBM. It is hypothesized that the composition of TME-associated cells will be different based on the therapy and therapeutic agents, and TME-targeting therapy will be better to decrease recurrence and improve survival. Therefore, the purpose of this study is to determine the changes in the TME in respect of T-cell population, M1 and M2 macrophage polarization status, and MDSC population following different treatments in a syngeneic model of GBM. In addition to these parameters, tumor growth and survival were also studied following different treatments. The results showed that changes in the TME-associated cells were dependent on the therapeutic agents, and the TME-targeting therapy improved the survival of the GBM bearing animals. The current GBM therapies should be revisited to add agents to prevent the accumulation of bone marrow-derived cells in the TME or to prevent the effect of immune-suppressive myeloid cells in causing alternative neovascularization, the revival of glioma stem cells, and recurrence. Instead of concurrent therapy, a sequential strategy would be better to target TME-associated cells.

Sign in / Sign up

Export Citation Format

Share Document